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01-04-2006 | Review Article

How to define follicular thyroid carcinoma?

Authors: Kurt Werner Schmid, Nadir Rashad Farid

Published in: Virchows Archiv | Issue 4/2006

Abstract

The appropriate diagnosis of follicular thyroid carcinoma (FTC) still depends on its histological discrimination from follicular adenoma (including the distinction of benign from malignant oncocytic variants), papillary thyroid carcinoma (particularly from the follicular variants) and poorly differentiated thyroid carcinoma. The use of immunohistochemical markers contributed only marginally to better defining FTC. The introduction of the micro array technique, however, may offer the possibility of getting a better insight into the natural history, as well as predicting the clinical course, of a given thyroid nodule. This review attempts to recapitulate common standards in the diagnosis of FTC, to summarise current molecular data available to distinguish FTC from other benign and malignant tumours and, finally, to outline future perspectives to define FTC on its specific genetic features.

Albores-Saavedra J, Gould E, Vardaman C, Vuitch F (1991) The macrofollicular variant of papillary thyroid carcinoma: a study of 17 cases. Hum Pathol 22:1195–1205CrossRefPubMed

Albores-Saavedra J, Carrick K (2004) Where to set the threshold between well differentiated and poorly differentiated follicular carcinomas of the thyroid. Endocr Pathol 15:297–305CrossRefPubMed

Aldred MA, Ginn-Pease ME, Morrison CD, Popkie AP, Gimm O, Hoang-Vu C, Krause U, Dralle H, Jhiang SM, Plass C, Eng C (2003) Caveolin-1 and caveolin-2, together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis. Cancer Res 63:2864–2871PubMed

Aldred MA, Huang Y, Liyanarachchi S, Pellegata NS, Gimm O, Jhiang S, Davuluri RV, de la Chapelle A, Eng C (2004) Papillary and follicular thyroid carcinomas show distinctly different microarray expression profiles and can be distinguished by a minimum of five genes. J Clin Oncol 22:3531–3539CrossRefPubMed

Anwar F, Emond MJ, Schmidt RA, Hwang HC, Bronner MP (2000) Retinoblastoma expression in thyroid neoplasms. Mod Pathol 13:562–569CrossRefPubMed

Apel RL, Ezzat S, Bapat BV, Pan N, LiVolsi VA, Asa SL (1995) Clonality of thyroid nodules in sporadic goiter. Diagn Mol Pathol 4:113–121PubMedCrossRef

Barden CB, Shister KW, Zhu B, Guiter G, Greenblatt DY, Zeiger MA, Fahey TJ 3rd (2003) Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin Cancer Res 9:1792–1800PubMed

Baris O, Savagner F, Nasser V, Loriod B, Granjeaud S, Guyetant S, Franc B, Rodien P, Rohmer V, Bertucci F, Birnbaum D, Malthiery Y, Reynier P, Houlgatte R (2004) Transcriptional profiling reveals coordinated up-regulation of oxidative metabolism genes in thyroid oncocytic tumors. J Clin Endocrinol Metab 89:994–1005CrossRefPubMed

Baris O, Mirebeau-Prunier D, Savagner F, Rodien P, Ballester B, Loriod B, Granjeaud S, Guyetant S, Franc B, Houlgatte R, Reynier P, Malthiery Y (2005) Gene profiling reveals specific oncogenic mechanisms and signaling pathways in oncocytic and papillary thyroid carcinoma. Oncogene 24:4155–4461PubMed

10.

Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vecchione A, Tecce R, Larsson O (2001) Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–1650CrossRefPubMed

11.

Berho M, Suster S (1997) The oncocytic variant of papillary carcinoma of the thyroid: a clinicopathologic study of 15 cases. Hum Pathol 28:47–53CrossRefPubMed

12.

Bronner MP, LiVolsi VA (1988) Oxyphilic (Askanazy/Hürthle cell) tumors of the thyroid: microscopic features predict biological behaviour. Surg Pathol 1:137–150

13.

Canzian F, Amati P, Harach HR, Kraimps JL, Lesueur F, Barbier J, Levillain P, Romeo G, Bonneau D (1998) A gene predisposing to familial thyroid tumors with cell oxyphilia maps to chromosome 19p13.2. Am J Hum Genet 63:1743–1748CrossRefPubMed

14.

Carcangiu ML, Zampi G, Rosai J (1984) Poorly differentiated (“insular”) thyroid carcinoma. A reinterpretation of Langhans’ “wuchernde Struma”. Am J Surg Pathol 8:655–668PubMedCrossRef

15.

Carcangiu ML, Bianchi S, Savino D, Voynick IM, Rosai J (1991) Follicular Hurthle cell tumors of the thyroid gland. Cancer 68:1944–1953PubMedCrossRef

16.

Cerutti JM, Delcelo R, Amadei MJ, Nakabashi C, Maciel RM, Peterson B, Shoemaker J, Riggins GJ (2004) A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. J Clin Invest 113:1234–1242CrossRefPubMed

17.

Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL (2001) Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 14:338–342CrossRefPubMed

18.

Chevillard S, Ugolin N, Vielh P, Ory K, Levalois C, Elliott D, Clayman GL, El-Naggar AK (2004) Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications. Clin Cancer Res 10:6586–6597PubMedCrossRef

19.

Chung DH, Kang GH, Kim WH, Ro JY (1999) Clonal analysis of a solitary follicular nodule of the thyroid with the polymerase chain reaction method. Mod Pathol 12:265–271PubMed

20.

D’Avanzo A, Treseler P, Ituarte PH, Wong M, Streja L, Greenspan FS, Siperstein AE, Duh QY, Clark OH (2004) Follicular thyroid carcinoma: histology and prognosis. Cancer 100:1123–1129CrossRefPubMed

21.

Evans HL, Vassilopoulou-Sellin R (1998) Follicular and Hurthle cell carcinomas of the thyroid: a comparative study. Am J Surg Pathol 22:1512–1520CrossRefPubMed

22.

Finley DJ, Zhu B, Barden CB, Fahey TJ III (2004) Discrimination of benign and malignant thyroid nodules by molecular profiling. Ann Surg 240:425–437PubMedCrossRef

23.

Garcia-Rostan G, Camp RL, Herrero A, Carcangiu ML, Rimm DL, Tallini G (2001) Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis. Am J Pathol 158:987–996PubMed

24.

Garcia-Rostan G, Zhao H, Camp RL, Pollan M, Herrero A, Pardo J, Wu R, Carcangiu ML, Costa J, Tallini G (2003) ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 21:3226–3235CrossRefPubMed

25.

Harach HR, Lesueur F, Amati P, Brown A, Canzian F, Kraimps JL, Levillain P, Menet E, Romeo G, Bonneau D (1999) Histology of familial thyroid tumours linked to a gene mapping to chromosome 19p13.2. J Pathol 189:387–393CrossRefPubMed

26.

Harrer P, Broecker M, Zint A, Schatz H, Zumtobel V, Derwahl M (1998) Thyroid nodules in recurrent multinodular goiters are predominantly polyclonal. J Endocrinol Invest 21:380–385PubMed

27.

Hedinger C, Williams ED, Sobin LH (1988) Histological typing of thyroid tumours. International histological classification of tumours. Springer, Berlin Heidelberg New York

28.

Hofstädter F (1980) Frequency and morphology of malignant tumours of the thyroid before and after the introduction of iodine-prophylaxis. Virchows Arch A Pathol Anat Histol 385:263–270CrossRefPubMed

29.

Johnson TL, Lloyd RV, Burney RE, Thompson NW (1987) Hurthle cell thyroid tumors. An immunohistochemical study. Cancer 59:107–112PubMedCrossRef

30.

Katoh R, Harach HR, Williams ED (1998) Solitary, multiple, and familial oxyphil tumours of the thyroid gland. J Pathol 186:292–299CrossRefPubMed

31.

Kesmodel SB, Terhune KP, Canter RJ, Mandel SJ, LiVolsi VA, Baloch ZW, Fraker DL (2003) The diagnostic dilemma of follicular variant of papillary thyroid carcinoma. Surgery 134:1005–1012CrossRefPubMed

32.

Kober F, Wolf G, Depisch D, Galvan G, Keminger K, Ladurner D, Langsteger W, Ogris E, Pimpl W, Roka R, Schmalzer E, Schmid KW, Tuchmann A (1990) Schilddrüsenkarzinom. In: Steindorfer P (ed) Manual der chirurgischen Krebstherapie. Springer, Berlin Heidelberg New York, pp 35–48

33.

Krohn K, Paschke R (2002) Somatic mutations in thyroid nodular disease. Mol Genet Metab 75:202–208CrossRefPubMed

34.

Lang W, Choritz H, Hundeshagen H (1986) Risk factors in follicular thyroid carcinomas. A retrospective follow-up study covering a 14-year period with emphasis on morphological findings. Am J Surg Pathol 10:246–255PubMedCrossRef

35.

LiVolsi VA (1990) Surgical pathology of the thyroid. Major problems in pathology, vol 22. Saunders, Philadelphia

36.

LiVolsi VA (2003) Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival. Cancer 98:1997–1998CrossRefPubMed

37.

Ljungberg O, Bondeson L, Bondeson AG (1984) Differentiated thyroid carcinoma, intermediate type: a new tumor entity with features of follicular and parafollicular cell carcinoma. Hum Pathol 15:218–228PubMedCrossRef

38.

Mai KT, Elmontaser G, Perkin DG, Thomas J, Stinson WA (2005) Benign Hürthle cell adenoma with papillary architecture: a benign lesion mimicking oncocytic papillary carcinoma. Int J Surg Pathol 13:37–41PubMedCrossRef

39.

Marques AR, Espadinha C, Frias MJ, Roque L, Catarino AL, Sobrinho LG, Leite V (2004) Underexpression of peroxisome proliferator-activated receptor (PPAR)gamma in PAX8/PPARgamma-negative thyroid tumours. Br J Cancer 91:732–738PubMed

40.

Maximo V, Sores P, Rocha AS, Sobrinho-Simoes M (1998) The common deletion of mitochondrial DNA is found in goiters and thyroid tumors with and without oxyphil cell change. Ultrastruc Pathol 22:271–273

41.

Maximo V, Sobrinho-Simoes M (2000) Hurthle cell tumours of the thyroid. A review with emphasis on mitochondrial abnormalities with clinical relevance. Virchows Arch 437:107–115CrossRefPubMed

42.

Maximo V, Soares P, Lima J, Cameselle-Teijeiro J, Sobrinho-Simoes M (2002) Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hurthle cell tumors. Am J Pathol 160:1857–1865PubMed

43.

Maximo V, Botelho T, Capela J, Soares P, Lima J, Taveira A, Amaro T, Barbosa AP, Preto A, Harach HR, Williams D, Sobrinho-Simoes M (2005) Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer 92:1892–1898CrossRefPubMed

44.

Mazzanti C, Zeiger MA, Costouros NG, Umbricht C, Westra WH, Smith D, Somervell H, Bevilacqua G, Alexander HR, Libutti SK (2004) Using gene expression profiling to differentiate benign versus malignant thyroid tumors. Cancer Res 64:2898–2903CrossRefPubMed

45.

McDonald MP, Sanders LE, Silverman ML, Chan HS, Buyske J (1996) Hurthle cell carcinoma of the thyroid gland: prognostic factors and results of surgical treatment. Surgery 120:1000–1004PubMedCrossRef

46.

Mendelsohn G (1988) Pathology of thyroid disease. In: Mendelsohn G (ed) Diagnosis and pathology of endocrine disease. J.B. Lippincott, Philadelphia, pp 37–117

47.

Miyake N, Maeta H, Horie S, Kitamura Y, Nanba E, Kobayashi K, Terada T (2001) Absence of mutations in the beta-catenin and adenomatous polyposis coli genes in papillary and follicular thyroid carcinomas. Pathol Int 51:680–685CrossRefPubMed

48.

Müller-Hocker J, Jacob U, Seibel P (1998) Hashimoto thyroiditis is associated with defects of cytochrome-c oxidase in oxyphil Askanazy cells and with the common deletion (4,977) of mitochondrial DNA. Ultrastruct Pathol 22:91–100PubMedCrossRef

49.

Musholt PB, Imkamp F, von Wasielewski R, Schmid KW, Musholt TJ (2003) RET rearrangements in archival oxyphilic thyroid tumors: new insights in tumorigenesis and classification of Hurthle cell carcinomas? Surgery 134:881–889CrossRefPubMed

50.

Nesland JM, Sobrinho-Simoes MA, Holm R, Sambade MC, Johannessen JV (1985) Hurthle-cell lesions of the thyroid: a combined study using transmission electron microscopy, scanning electron microscopy, and immunocytochemistry. Ultrastruct Pathol 8:269–290PubMed

51.

Nibu K-I, Otsuko N, Nakao K, Sugasawa M, Rothstein JL (2005) RET/PTC fusion gene rearrangements in Japanese thyroid carcinomas. Eur Arch Otorhinolaryngol 262:368–373CrossRefPubMed

52.

Nikiforov YE (2004) Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinoma. Endocr Pathol 15:319–327CrossRefPubMed

53.

Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW, Tallini G, Kroll TG, Nikiforov YE (2003) Ras point mutations and PAX8-PPAR gamma rearrangements in thyroid tumours: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 88:2318–2326CrossRefPubMed

54.

Papotti M, Botto Micca F, Favero A, Palestini N, Bussolati G (1993) Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns. Am J Surg Pathol 17:291–301PubMedCrossRef

55.

Papotti M, Torchio B, Grassi L, Favero A, Bussolati G (1996) Poorly differentiated oxyphilic (Hurthle cell) carcinomas of the thyroid. Am J Surg Pathol 20:686–694CrossRefPubMed

56.

Pilotti S, Collini P, Mariani L, Placucci M, Bongarzone I, Vigneri P, Cipriani S, Falcetta F, Miceli R, Pierotti MA, Rilke F (1997) Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland. Am J Surg Pathol 21:1466–1473CrossRefPubMed

57.

Puskas LG, Farid NR (2004) Gene expression in thyroid tumors. In: Farid NR (ed) The molecular basis of thyroid cancer. Kluwer, Boston, pp 265–271

58.

Puskas LG, Juhasz F, Farid NR (2004) Microarray study of malignant and benign nodular thyroid tissue. In: 86th annual meeting of the Endocrine Society, Abstract P2, New Orleans, p 183

59.

Puskas LG, Juhasz F, Zarva A, Hackler L Jr, Farid NR (2005) Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors. Mol Cell Biol 51:177–186

60.

Raphael SJ (2002) The meanings of markers: ancillary techniques in diagnosis of thyroid neoplasia. Endocr Pathol 13:301–311CrossRefPubMed

61.

Rosai J, Carcangiu ML, DeLellis RA (1992) Tumors of the thyroid gland. Atlas of tumor pathology, 3rd series, vol 5. AFIP, Washington, DC

62.

Rosai J (2004) Poorly differentiated thyroid carcinoma: introduction to the issue, its landmarks, and clinical impact. Endocr Pathol 15:293–296CrossRefPubMed

63.

Sakamoto A, Kasai N, Sugano H (1983) Poorly differentiated carcinoma of the thyroid. A clinicopathologic entity for a high-risk group of papillary and follicular carcinomas. Cancer 52:1849–1855PubMedCrossRef

64.

Schmid KW, Tötsch M, Hittmair A, Feichtinger H, Ladurner D, Hofstädter F (1989) Frequency of medullary thyroid carcinoma in an endemic area. Mod Pathol 2:90–93PubMed

65.

Schmid KW, Tötsch M, Öfner D, Böcker W, Ladurner D (1997) Minimally invasive follicular thyroid carcinoma. A clinico-pathological study. In: Schmid KW, Böcker W (eds) Thyroid pathology. Current topics in pathology. Springer, Berlin Heidelberg New York, pp 37–44

66.

Schmid KW (1998) Does the encapsulated oxyphilic variant of papillary thyroid carcinoma really exist? J Pathol 184:31ACrossRef

67.

Schmid KW, Sheu S-Y, Görges R, Ensinger C, Tötsch M (2003) Tumoren der Schilddrüse. Pathologe 24:357–372CrossRefPubMed

68.

Schröder S (1988) Pathologie und Klinik maligner Schilddrüsentumoren. Gustav Fischer Verlag, Stuttgart

69.

Shaha AR, Loree TR, Shah JP (1995) Prognostic factors and risk group analysis in follicular carcinoma of the thyroid. Surgery 118:1131–1136PubMedCrossRef

70.

Shahedian B, Shi Y, Zou M, Farid NR (2001) Thyroid carcinoma is characterized by genomic instability: evidence from p53 mutations. Mol Genet Metab 72:155–163CrossRefPubMed

71.

Shi Y, Zou M, Varkondi E, Nagy A, Kozma L, Farid NR (2001) Cyclin D1 in thyroid carcinomas. Thyroid 10:741–746

72.

Sneed DC (1999) Protocol for the examination of specimens from patients with malignant tumors of the thyroid gland, exclusive of lymphomas. Arch Pathol Lab Med 123:45–49PubMed

73.

Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Maximo V, Botelho T, Seruca R, Sobrinho-Simoes M (2003) BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 22:4578–4580CrossRefPubMed

74.

Sobrinho-Simoes MA, Nesland JM, Holm R, Sambade MC, Johannessen JV (1985) Hurthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study. Ultrastruct Pathol 8:131–142PubMed

75.

Sobrinho-Simoes M, Maximo V, Castro IV, Fonseca E, Soares P, Garcia-Rostan G, Oliveira MC (2005) Hurthle (oncocytic) cell tumors of thyroid: etiopathogenesis, diagnosis and clinical significance. Int J Surg Pathol 13:29–35PubMedCrossRef

76.

Stewart BW, Kleihues P (2003) World cancer report. IARC Press, Lyon, pp 257–260

77.

Takano T, Miyauchi A, Yoshida H, Kuma K, Amino N (2004) High-throughput differential screening of mRNAs by serial analysis of gene expression: decreased expression of trefoil factor 3 mRNA in thyroid follicular carcinomas. Br J Cancer 90:1600–1605CrossRefPubMed

78.

Takano T, Miyauchi A, Yoshida H, Kuma K, Amino N (2005) Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma. Cancer Lett 219:91–96CrossRefPubMed

79.

Tallini G (1998) Oncocytic tumours. Virchows Arch 433:5–12CrossRefPubMed

80.

Thomas D, Lizyness M, Kuick R, Sanders D, Misek D, Hanash S, Nikiforov Y, Koenig R, Giorando TJ (2004) Gene expression signature of oncocytic (Hurthle cell) thyroid carcinoma. Thyroid 14:713

81.

Thomas GA, Williams D, Williams ED (1989) The clonal origin of thyroid nodules and adenomas. Am J Pathol 134:141–147PubMed

82.

Trovisco V, Soares P, Preto A, de Castro IV, Lima J, Castro P, Maximo V, Botelho T, Moreira S, Meireles AM, Magalhaes J, Abrosimov A, Cameselle-Teijeiro J, Sobrinho-Simoes M (2005) Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients’ age but not with tumour aggressiveness. Virchows Arch 446:589–595CrossRefPubMed

83.

Valenta LJ, Michel-Bechet M, Warshaw JB, Maloof F (1974) Human thyroid tumors composed of mitochondrion-rich cells: electron microscopic and biochemical findings. J Clin Endocrinol Metab 39:719–733PubMedCrossRef

84.

Vickery AL Jr, Carcangiu ML, Johannessen JV, Sobrinho-Simoes M (1985) Papillary carcinoma. Semin Diagn Pathol 2:90–100PubMed

85.

Volante M, Landolfi S, Chiusa L, Palestini N, Motta M, Codegone A, Torchio B, Papotti MG (2004) Poorly differentiated carcinomas of the thyroid with trabecular, insular, and solid patterns: a clinicopathologic study of 183 patients. Cancer 100:950–957CrossRefPubMed

86.

Volante M, Cavallo GP, Papotti M (2004) Prognostic factors of clinical interest in poorly differentiated carcinomas of the thyroid. Endocr Pathol 15:313–317CrossRefPubMed

87.

Watson RG, Brennan MD, Goellner JR, van Heerden JA, McConahey WM, Taylor WF (1984) Invasive Hurthle cell carcinoma of the thyroid: natural history and management. Mayo Clin Proc 59:851–855PubMed

88.

Weber F, Shen L, Aldred MA, Morrison CD, Frilling A, Saji M, Schuppert F, Broelsch CE, Ringel MD, Eng C (2005) Genetic classification of benign and malignant follicular neoplasm based on a 3-gene combination. J Clin Endocrinol Metab 90:2512–2521CrossRefPubMed

89.

DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) (2004) WHO histological classification of thyroid and parathyroid tumours. World Health Organization classification of tumours. Pathology & genetics. Tumours of endocrine organs. IARC Press, Lyon, pp 49–123

90.

Williams ED, Doniach I, Bjarnson O, Michie W (1977) Thyroid cancer in an iodine rich area. Cancer 39:215–222PubMedCrossRef

91.

Williams ED (2000) Guest editorial: two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol 8:181–183PubMedCrossRef

92.

Wynford-Thomas D (1994) Thyroid cancer. In: Lemoine N, Neoptolemos J, Cooke T (eds) Cancer. A molecular approach. Blackwell Scientific Publications, Oxford, pp 192–222

93.

Yano Y, Uematsu N, Yashiro T, Hara H, Ueno E, Miwa M, Tsujimoto G, Aiyoshi Y, Uchida K (2004) Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma. Clin Cancer Res 10:2035–2043CrossRefPubMed

Title: How to define follicular thyroid carcinoma?
Authors: Kurt Werner Schmid
Nadir Rashad Farid
Publication date: 01-04-2006
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 4/2006
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-006-0162-0

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